Boron-containing aptamers to ATP
Boron-containing aptamers to ATP
复制标题
DOI：
10.1093/nar/30.6.1401
复制
发表时间：
2002-03-15
影响因子：
14.9
通讯作者：
Burke, DH
中科院分区：
文献类型：
--
作者：
Lato, SM;Ozerova, NDS;Burke, DH
硼中子捕获疗法（BNCT）是一种针对某些癌症的实验性治疗方法，仅破坏硼附近的细胞；然而，需要开发高度特异性的递送剂。由于核酸适体识别特定的分子靶标，我们通过指数富集 (SELEX) 过程研究了硼化核苷酸类似物对 RNA 功能和配体系统进化的影响。在几种已知适体中，用鸟苷 5'-(α-P-硼酸) 三磷酸 (bG) 替代 GTP，或用尿苷 5'-(α-P-硼酸) 三磷酸 (bU) 替代 UTP，从而减少或消除了这些 RNA 的靶标识别。具体而言，含有 zeta 折叠的 ATP 结合适体（出现在腺苷适体的几种选择中）在 bG 取代后变得失活，但仅受到 bU 取代的中度影响。使用 bG 或 bU 类似物以及 C8 连接的 ATP 琼脂糖作为结合靶标进行选择。 bU 和正常 NTP 的选择产生了一些 zeta 折叠适体，而 bG 选择则没有产生这种类型。来自 bU 和 bG 群体的非 zeta 适体可以耐受硼烷取代，并且许多人需要它。硼烷核苷酸的要求是特定的； bl 不能用于 bG 依赖性适体，反之亦然。硼酸基团在靶标识别或 RNA 结构中发挥着重要作用，但尚未明确。我们得出结论，bG 和 bU 核苷酸与 SELEX 完全兼容，并且这些类似物可用于制造硼化适体作为 BNCT 的治疗剂。
Boron neutron capture therapy (BNCT), an experimental treatment for certain cancers, destroys only cells near the boron; however, there is a need to develop highly specific delivery agents. As nucleic acid aptamers recognize specific molecular targets, we investigated the influence of boronated nucleotide analogs on RNA function and on the systematic evolution of ligands by exponential enrichment (SELEX) process. Substitution of guanosine 5'-(alpha-P-borano) triphosphate (bG) for GTP or uridine 5'-(alpha-P-borano) triphosphate (bU) for UTP in several known aptamers diminished or eliminated target recognition by those RNAs. Specifically, ATP-binding aptamers containing the zeta-fold, which appears in several selections for adenosine aptamers, became inactive upon bG substitution but were only moderately affected by bU substitution. Selections were carried out using the bG or bU analogs with C8-linked ATP agarose as the binding target. The selections with bU and normal NTP yielded some zeta-fold aptamers, while the bG selection yielded none of this type. Non-zeta aptamers from bU and bG populations tolerated the borano substitution and many required it. The borano nucleotide requirement is specific; bl could not be used in bG-dependent aptamers nor vice versa. The borano group plays an essential role, as yet undefined, in target recognition or RNA structure. We conclude that the bG and bU nucleotides are fully compatible with SELEX, and that these analogs could be used to make boronated aptamers as therapeutics for BNCT.